The scavenger receptors (SRs) are a group of surveillance proteins that play important roles in immune defense. These proteins are divided into 12 classes (A–L) on the basis of their diverse structures and functions. Their differences enable SRs to interact with a vast array of pathogenic factors, such as bacteria, to induce appropriate responses. Multiple SR types can bind to the same pathogenic signals, and an individual SR can bind multiple signal types. Furthermore, SRs can reversibly interact with co-receptor proteins to launch various responses, highlighting the complex and dynamic nature of SR-related defense. In general, SRs control the recruitment and activation of immune cells that eat harmful substances, and they can either induce or suppress inflammation depending on the conditions. Many SRs have both membrane-bound and soluble forms that accomplish their scavenging functions, while one potential SR, ACE-2, appears to scavenge only in its soluble form. Although much has been discovered, more comprehensive research is needed to unravel the complicated defensive tactics of SRs and to enable therapeutic targeting of SRs in order to combat inflammatory and autoimmune diseases.